U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H26F3N3OS.2ClH
Molecular Weight 510.4452
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLUPHENAZINE HYDROCHLORIDE

SMILES

c1ccc2c(c1)N(CCCN3CCN(CC3)CCO)c4cc(ccc4S2)C(F)(F)F.Cl.Cl

InChI

InChIKey=MBHNWCYEGXQEIT-UHFFFAOYSA-N
InChI=1S/C22H26F3N3OS.2ClH/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29;;/h1-2,4-7,16,29H,3,8-15H2;2*1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H26F3N3OS
Molecular Weight 437.5235
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including

Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Originator

Curator's Comment:: Introduced in 1959

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FLUPHENAZINE DECANOATE

Approved Use

Fluphenazine Decanoate Injection is a long­acting parenteral antipsychotic drug intended for use in the management of patients requiring prolonged parenteral neuroleptic therapy (e.g., chronic schizophrenics).

Launch Date

5.5313282E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.3 ng/mL
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
261 ng/mL
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.52 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6.92 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.4 h
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.3 h
2.5 mg 3 times / 3 days multiple, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLUPHENAZINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.6%
FLUPHENAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Disc. AE: Akathisia, Dyskinesia...
AEs leading to
discontinuation/dose reduction:
Akathisia (3.3%)
Dyskinesia (3.3%)
Hypertonia (3.3%)
Stupor (3.3%)
Sources: Page: p.315
250 mg 1 times / week multiple, intramuscular
Highest studied dose
Dose: 250 mg, 1 times / week
Route: intramuscular
Route: multiple
Dose: 250 mg, 1 times / week
Sources: Page: p.1438
unhealthy, 44
n = 25
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 44
Sex: M+F
Population Size: 25
Sources: Page: p.1438
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Disc. AE: Tardive dyskinesia, Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Tardive dyskinesia
Neuroleptic malignant syndrome
Fall
Sources:
AEs

AEs

AESignificanceDosePopulation
Akathisia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Dyskinesia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Hypertonia 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Stupor 3.3%
Disc. AE
21 mg 1 times / day multiple, intramuscular (max)
Recommended
Dose: 21 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 21 mg, 1 times / day
Sources: Page: p.315
unhealthy, 35.4+/-10.4
n = 30
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35.4+/-10.4
Sex: M+F
Population Size: 30
Sources: Page: p.315
Fall Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Tardive dyskinesia Disc. AE
100 mg single, intramuscular|subcutaneous
Recommended
Dose: 100 mg
Route: intramuscular|subcutaneous
Route: single
Dose: 100 mg
Sources:
unhealthy
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Psuedotetanus caused by neuroleptics. Description of a case caused by fluphenazine].
1966 Sep-Oct
Side-effects of phenothiazines.
1967 Apr 1
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Side effects of parenteral long-acting phenothiazines.
1972 Jan 22
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
The effect of 5-hydroxytrytamine synthesis inhibitors on neuroleptic-induced catalepsy in rats.
1975
Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy.
1975 Jan-Feb
High vs standard dosage fluphenazine HCL in acute schizophrenia.
1978 Nov
Phenothiazine-induced dystonic reaction while swimming.
1978 Oct 21
Sleep disturbance associated with fluphenazine HCl: a case report.
1979 Jul
Benztropine prophylaxis of dystonic reactions.
1979 Mar 28
behavior of rats and mice administered active metabolites of fluphenazine, 7-hydroxy-fluphenazine and fluphenazine-sulfoxide.
1980 Nov
Fluphenazine pharmacokinetics and therapeutic response.
1981
Neuroleptic-induced acute dyskinesias in rhesus monkeys.
1981
Intrauterine effect of phenothiazines.
1981 Apr 18
Neuroleptic-induced seizures. An in vitro technique for assessing relative risk.
1982 Feb
Sexual dysfunction in women using major tranquilizers.
1982 Sep
A case of neuroleptic malignant syndrome successfully treated with amantadine.
1982 Sep
Occurrence of neuroleptic malignant syndrome in a narcoleptic patient.
1983 Jun
Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes.
1984 Sep
[Repeated acute dystonia following administration of metoclopramide and fluphenazine].
1988 Mar 14
[Tardive dystonia--a case report on therapy and metaphylaxis].
1988 May
Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment.
1990 Aug
Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.
1991
Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.
1991
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia.
1992
Nerve growth factor-stimulated calcium uptake into PC12 cells: uniqueness of the channel and evidence for phosphorylation.
1992 Apr
Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex.
1993 Sep-Dec
Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients.
1994 Jan
Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.
1995 Jul-Aug
Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.
1995 Nov-Dec
Roxindole, a potential antidepressant. I. Effect on the dopamine system.
1996
Tardive dyskinesia induced by risperidone?
1996 Jun
The anticataleptic effect of 7-OH-DPAT: are dopamine D3 receptors involved?
1999
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs.
2003 Mar
Analysis of phenothiazine and its derivatives using LC/electrochemistry/MS and LC/electrochemistry/fluorescence.
2003 Sep 15
Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior.
2004 Feb 18
Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.
2005 Sep 1
The neuroleptic drug, fluphenazine, blocks neuronal voltage-gated sodium channels.
2006 Aug 23
Series of seizures as a sign of development of recurrent malignant neuroleptic syndrome - a case report.
2006 Jun
Neuroleptic-induced dysphagia: case report and literature review.
2007 Jan
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs.
2007 Jul 17
Effects of omega-3 essential fatty acids (omega-3 EFAs) on motor disorders and memory dysfunction typical neuroleptic-induced: behavioral and biochemical parameter.
2010 Apr
Long-acting injectable antipsychotics: focus on olanzapine pamoate.
2010 Jun 24
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Antitubercular pharmacodynamics of phenothiazines.
2013 Apr
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: Fluphenazine Decanoate Injection may be given IM or SC
For most patients, a dose of 12.5 to 25 mg (0.5 to 1 mL) may be given to initiate therapy.
Route of Administration: Intramuscular
In Vitro Use Guide
30uM Fluphenazine inhibited the high-threshold Ca2 channel current in rat sympathetic neurons (blocking by 66%).
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:55:34 UTC 2021
Edited
by admin
on Fri Jun 25 20:55:34 UTC 2021
Record UNII
ZOU145W1XL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUPHENAZINE HYDROCHLORIDE
JAN   MART.   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
ANATENSOL
Common Name English
1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-10H-PHENOTHIAZIN-10-YL)PROPYL)-, DIHYDROCHLORIDE
Common Name English
FLUPHENAZINE HCL
Common Name English
FLUPHENAZINE HYDROCHLORIDE [VANDF]
Common Name English
SQUIBB 4918
Code English
FLUPHENAZINE DIHYDROCHLORIDE [MI]
Common Name English
DAPOTUM
Common Name English
FLUPHENAZINI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
PERMITIL
Brand Name English
FLUPHENAZINE DIHYDROCHLORIDE
EP   MI  
Common Name English
NSC-179197
Code English
FLUPHENAZINE HYDROCHLORIDE [USP]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [MART.]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [JAN]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [WHO-DD]
Common Name English
4-(3-(2-(TRIFLUOROMETHYL)PHENOTHIAZIN-10-YL)PROPYL)-1-PIPERAZINEETHANOL DIHYDROCHLORIDE
Systematic Name English
FLUPHENAZINE HYDROCHLORIDE [USP-RS]
Common Name English
PROLIXIN
Brand Name English
FLUPHENAZINE HYDROCHLORIDE [WHO-IP]
Common Name English
FLUPHENAZINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
205-674-1
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
EVMPD
SUB02232MIG
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
DRUG BANK
DBSALT000288
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
PUBCHEM
67356
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
MERCK INDEX
M5490
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C47995
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
CAS
146-56-5
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
ChEMBL
CHEMBL726
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
USP_CATALOG
1282004
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY USP-RS
WHO INTERNATIONAL PHARMACOPEIA
FLUPHENAZINE HYDROCHLORIDE
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY Description: A white or almost white, crystalline powder; odourless. Solubility: Soluble in 10 parts of water; sparingly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Neuroleptic.Storage: Fluphenazine hydrochloride should be kept in a well-closed container, protected from light. Additional information: Even in the absence of light, Fluphenazine hydrochloride is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Fluphenazine hydrochloride contains not less than 98.5% and not more than 101.5% of C22H26F3N3OS,2HCl, calculated with reference to the dried substance.
FDA UNII
ZOU145W1XL
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY
RXCUI
203207
Created by admin on Fri Jun 25 20:55:34 UTC 2021 , Edited by admin on Fri Jun 25 20:55:34 UTC 2021
PRIMARY RxNorm
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Related Record Type Details
IMPURITY -> PARENT
at 260 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
274 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
at 260 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
274 nm
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY